PROJECT SUMMARY ? OVERALL HIV-associated neurocognitive disorders (HAND) remain very prevalent, even among aviremic HIV+ individuals treated with CART. In the era of CART, the prevalence of HAND in HIV+ individuals with advanced infection remains around 40-50% [1, 2], and HAND may now be the most common form of young-age neurocognitive impairment globally [1]. Currently there are no uniformly accepted clinical, neuroimaging, or laboratory outcome measures for clinical trials for the treatment of HAND. HIV-related neuroscience research at Johns Hopkins University has focused on this challenging problem, exploring critical pathogenic mechanisms for neurological damage. Despite tremendous efforts to understand the mechanisms underlying the persistence of HAND, no definitive adjunctive therapeutics have yet entered clinical practice. There is also an unfilled need to develop surrogate markers and more robust and simpler screening instruments for HAND, to allow for earlier detection, for tracking of the course of HAND, and improving the efficiency of clinical trials. Until the NIMH Center was established at JHU collaborations had been limited by the lack of a central organizing structure for this type of research, and limited resources to facilitate cross-disciplinary and translational research. The JHU NIMH Center has addressed these needs over the past 11 years and has provided a resource to catalyze interdisciplinary research in HIV neuroscience, with the aim of leading to new therapies. Accomplishments of the Center are highlighted in the Overall Strategy section and in each individual core, and the key accomplishment is our proven ability to move HAND therapeutics from the discovery phase, through animal models, and on to clinical trials, with the ultimate goal of shifting clinical practice.